背景:青春期暴饮暴食是以后生活中有问题的酒精(乙醇)消耗的危险因素,然而,通过乙醇自我给药模拟这种现象的小鼠研究提供了不同的发现。青春期sigma-1受体(S1-R)系统的拮抗作用可调节乙醇的动机效应和摄入量。它仍然是未知的,然而,这种拮抗作用是否可以防止青少年暴饮暴食后成年期的乙醇摄入量增加。
方法:实验。1和2测试了成年雄性或雌性Wistar大鼠-在青春期(出生后第31-49天;九个2小时的2小时获取8-10%乙醇)-使用24小时两瓶选择测试(实验。1)或时间限制,单瓶,测试(实验。2).实验2-5评估,在青少年或成年大鼠中,S1-R拮抗剂S1RA对乙醇摄入和乙醇诱导的条件味道或位置厌恶的影响。辅助测试(例如,新颖的物体识别,还进行了乙醇诱导的运动活动)。
结果:青少年乙醇暴露促进乙醇消耗,单瓶,在成年期进行的两瓶选择测试中。S1RA给药减少了成年时的乙醇摄入量,并促进了乙醇诱导的味觉(但不是地方)厌恶的发展。
结论:S1RA有望减少青春期慢性和大量乙醇暴露后的乙醇摄入量,从而导致成年期乙醇暴露增加。S1-R拮抗作用的这种假定保护作用可能与S1RA加剧了该药物的厌恶作用有关。
BACKGROUND: Binge drinking at adolescence is a risk factor for problematic alcohol (ethanol) consumption later in life, yet the murine studies that modelled this phenomenon via ethanol self-administration have provided mixed findings. Antagonism of the sigma-1 receptor (S1-R) system at adolescence modulates ethanol\'s motivational effects and intake. It is still unknown, however, whether this antagonism would protect against enhanced ethanol intake at adulthood after adolescent binge ethanol exposure.
METHODS: Exp. 1 and 2 tested adults male or female Wistar rats -exposed or not to ethanol self-administration at adolescence (postnatal days 31-49; nine 2-hour sessions of access to 8-10% ethanol)- for ethanol intake using 24-h two-bottle choice test (Exp. 1) or time restricted, single-bottle, tests (Exp. 2). Experiments 2-5 evaluated, in adolescent or adult rats, the effects of the S1-R antagonist S1RA on ethanol intake and on ethanol-induced conditioned taste or place aversion. Ancillary tests (e.g., novel object recognition, ethanol-induced locomotor activity) were also conducted.
RESULTS: Adolescent ethanol exposure promoted ethanol consumption at both the restricted, single-bottle, and at the two-bottle choice tests conducted at adulthood. S1RA administration reduced ethanol intake at adulthood and facilitated the development of ethanol-induced taste (but not place) aversion.
CONCLUSIONS: S1RA holds promise for lessening ethanol intake after chronic and substantial ethanol exposure in adolescence that results in heightened ethanol exposure at adulthood. This putative protective effect of S1-R antagonism may relate to S1RA exacerbating the aversive effects of this drug.